title: Protein cage nanoparticles bearing the LyP-1 peptide for enhanced imaging of macrophage-rich vascular lesions.
abstract: Cage-like protein nanoparticles are promising platforms for cell- and tissue-specific targeted delivery of imaging and therapeutic agents. Here, we have successfully modified the 12 nm small heat shock protein from Methanococcus jannaschii (MjHsp) to detect atherosclerotic plaque lesions in a mouse model system. As macrophages are centrally involved in the initiation and progression of atherosclerosis, targeted imaging of macrophages is valuable to assess the biologic status of the blood vessel wall. LyP-1, a nine residue peptide, has been shown to target tumor-associated macrophages. Thus, LyP-1 was genetically incorporated onto the exterior surface of MjHsp, while a fluorescent molecule (Cy5.5) was conjugated on the interior cavity. This bioengineered protein cage, LyP-Hsp, exhibited enhanced affinity to macrophage in vitro. Furthermore, in vivo injection of LyP-Hsp allowed visualization of macrophage-rich murine carotid lesions by in situ and ex vivo fluorescence imaging. These results demonstrate the potential of LyP-1-conjugated protein cages as nanoscale platforms for delivery of imaging agents for the diagnosis of atherosclerosis.
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana 59717, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Uchida
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kosuge
authors.forename: Masahiro
authors.initials: M
authors.lastname: Terashima
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Willits
authors.forename: Lars O
authors.initials: LO
authors.lastname: Liepold
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Young
authors.forename: Michael V
authors.initials: MV
authors.lastname: McConnell
authors.forename: Trevor
authors.initials: T
authors.lastname: Douglas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D053758:Nanoparticles; D010446:Peptide Fragments / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D014652:Vascular Diseases / Q000473:pathology*
chemical_list: D005456:Fluorescent Dyes; C461500:LyP-1 protein, mouse; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011506:Proteins